tbuckley/cabot-search huggingface dataset:
PB2208: CLUSTER ANALYSIS UNVEILS THE CLINICAL SPECTRUM OF ERDHEIM-CHESTER DISEASE
Authors: Michelangelo Tesi, Francesco Pegoraro, Francesco Peyronel, Martina Mazzariol, Elena Gelain, Matthew Koster, Ronald Go, Gaurav Goyal, Matthew Collin, Paul Milne, Sarah Pagan, Fleur Cohen-Aubart, Matthias Papo, Juvianee Estrada-Veras, Roei Mazor, Lorenzo Dagna, Eli Diamond, Augusto Vaglio, Julien Haroche
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Erdheim-Chester Disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by tissue infiltration by foamy histiocytes. The disease is driven by mutations in proto-oncogenes such as BRAF, which activate mitogen-activated protein kinase (MAPK) pathways, while immune-mediated mechanisms contribute to disease development and progression. Clinical manifestations are extremely heterogeneous and virtually every organ system can be affected. Aims: In the present cohort study, we aimed at classifying patients with ECD based on clinical presentation and mutational status using an unsupervised data-driven clustering approach. Methods: This study was based on a dataset of 356 patients with ECD that contained data referred to demographics, clinical presentation, mutational status (BRAF and other relevant genes), and follow-up including treatment and outcome. Clinical features at presentation along with mutational status were included as twenty input variables in the clustering model. The dimensionality of the dataset was reduced through a principal component method, and then a hierarchical clustering approach was used. Each generated cluster was characterized by analyzing its summary features. Results: The clustering algorithm produced two models, one with four clusters and one with five. The generated clusters were labeled with their prominent features or given a representative name. The clusters named “Digestive/Hematologic/Myelodysplastic Syndrome” (around 3% of subjects), “Testis/Lymph Nodes/MAP2K1 mutation” (8%), and “Limited Disease” (30%) were identical across the two models. The remaining patients showed a high rate of BRAF mutation (around 90%) and were aggregated in a single large cluster named “Widespread Disease” (59%) in the four-cluster model, whereas they were split into two different clusters - the “Hypothalamic/Pituitary/Associated Langerhans Cell Histiocytosis” (25%) and the “Cardiovascular/Perirenal”(34%) - in the five-cluster model. Summary/Conclusion: Hierarchical clustering on principal components subdivided the ECD patient sample into clusters which reflect what has often already been observed in the clinical practice, with regard to the widespread disease phenotype as opposed to the limited one, and with regard to the phenotypes of ECD associated with other types of histiocytosis or myelodysplastic syndrome. Keywords: Patient, Real world data, Phenotype, Clinical data
PB2268: PAX5 ABERRANT EXPRESSION INCORPORATED IN MIPI-SP RISK SCORING SYSTEM EXHIBITS ADDITIVE VALUE IN MANTLE CELL LYMPHOMA
Authors: Xin Zhang, Yang Han, Yu Nie, Yujie Jiang, Xiaohui Sui, Xueling Ge, Fang Liu, Ya Zhang, Xin Wang
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin lymphoma with highly heterogeneous clinical courses. Paired-box 5 (PAX5), the regulator of B cell differentiation and growth, is abnormally expressed in several types of cancers. However, the explicit link between PAX5 alterations and prognosis of MCL patients still needs further investigation. Aims: This study aims to explore the role of PAX5 expression in MCL patients and establish a novel risk scoring system for clinical risk assessment in MCL. Methods: We comprehensively analyzed the clinical features and laboratory data of eighty-two MCL cases. Positive and negative PAX5 expression were distinguished by immunohistochemical staining. Kaplan-Meier and Cox regression were employed to investigate the effect of different factors on the prognosis of MCL patients. Furthermore, a novel risk score system was established based on multivariate Cox analysis and was evaluated through the area under the receiver operating characteristic (ROC) curve. Results: In MCL patients, PAX5 positivity was associated with shorter overall survival (OS; p=0.011) and was identified as an independent prognostic factor. Survival analysis of other clinical characteristics demonstrated that high-risk score (p=0.028), Mantle Cell Lymphoma International Prognostic Index (MIPI) score (p=0.006), high ECOG (≥2; p=0.019), splenomegaly (p=0.002) and high level of β2-MG (≥2.65 mg/L; p=0.002) were correlated with worse OS. Moreover, the elevated β2-MG (p=0.027) and advanced MIPI score (p=0.014) were related to positive PAX5 expression. In MCL patients with PAX5 positive expression, β2-MG (≥2.65 mg/L; p=0.042), splenomegaly (p=0.005), Ki67 positive rate (≥30%; p=0.047) and LDH (≥202 U/L; p=0.046) were correlated with inferior OS. The novel risk scoring system called MIPI-SP was established and exhibited a superior prognostic value for OS depending on an area under the ROC curve (AUC) of 0.770 (95% CI, 0.658-0.881) than MIPI score with an AUC of 0.698 (95% CI, 0.576-0.820). Summary/Conclusion: This study provides insight into the potential role of PAX5 in MCL, and the novel risk scoring system MIPI-SP optimizes the risk stratification and facilitates prognosis evaluation in MCL patients. Keywords: Immunohistochemistry, Mantle cell lymphoma
Developing a Clinical Cardio-Oncology Program and the Building Blocks for Success
Authors: Michael G. Fradley, Nicholas Wilcox, Irene Frain, Vijay U. Rao, Joseph Carver, Avirup Guha, Susan Dent
Journal: JACC CardioOncology (2023)

•Cardio-oncology programs are necessary to provide optimal cardiovascular care to cancer patients and survivors.•Focus on developing a clear vision and mission-successful programs must be tailored to an organization's unique landscape.•Fostering partnerships with cardiologists and oncologists to provide high-quality patient-centered care is crucial.•Patience is essential-program development takes time, but success can be achieved.
PB2363: R-MPV FOLLOWED BY CONSOLIDATION REDUCED-DOSE WHOLE-BRAIN RADIOTHERAPY AND CYTARABINE IN NEWLY DIAGNOSED PRIMARY CNS LYMPHOMA: REAL WORLD DATA
Authors: Maha EL Amani, Soukaina Haidouri, Apolinaire Afodome, Othman Doghmi, Oumayma Hari, Yossra Aghoutane, Naoufal Benlachgar, Majdouline Bououad, Zoubida Tazi Mezalek
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Primary CNS lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma that originates in the brain, cerebrospinal fluid, spinal cord, or eyes. Because the affected areas of the CNS differ from patient to patient, clinical signs and symptoms of the disease are variable, and diagnosis requires a high level of suspicion. Aims: We aim to report our data on the use of the R-MPV protocole (Rituximab, Methotrexate, Procarbazine, Vincristine) followed by a reduced dose whole-brain radiotherapy in the treatment of PCNSL in real word settings. Methods: This is a descriptive retrospective study conducted on 10 immunocompetent patients, at the clinical hematology department of the Ibn Sina teaching hospital in Rabat over 6 years (January 2017-September 2022). Results: In the cohort studied, the median age was 50 years [19 years – 78 years], with a M/F sex ratio of 0.6 [6 females – 4 males].The clinical examination found a deteriorated general condition in the majority of patients (50% of the patients had a PS score of 4, 20% had a PS score of 3). Four patients had a pyramidal syndrome, three a cerebellar syndrome, two had phasic disorders, one had a Parinaud’s syndrome and one had intracranial hypertension. Sus and sub-tentorial locations were the most common in imaging (30%). The anatomopathological study showed a diffuse large B cell lymphoma (DLBCL) non germinal centre type in 9 patients, and an NOS T cell lymphoma in one patient. The therapeutic protocol consisted in the administration of Rituximab for B cell lymphomas, associated to Methotrexate, Procarbazine and Vincristine (R-MPV), and MPV for T cell lymphoma. A reduced dose whole-brain radiotherapy (rdWBRT) consolidation and high dose Cytarabine was performed. Complete remission was achieved in 6 patients (2 after 5 R-MPV cycles and 4 after 7 cycles). The median follow-up was 15.7 months, and the overall survival (OS) was 50%. The overall response to treatment (OR) was 70%. Progression free survival (PFS) at 6 months was 60%, and at 12 months 50% (1 primary refractory patient, 1 relapse and 1 progression). The complications were mainly hematological toxicities, with 80% grade III-IV neutropenia and thrombopenia. Summary/Conclusion: Following our experience, an advanced age at diagnosis, low PS score and late diagnosis are poor prognosis factors. The R-MPV protocol associated to consolidation rdWBRT and Cytarabine was associated with high response rate and minimal neurotoxicity, even in elderly patients. Keywords: Radiotherapy, Non-Hodgkin’s lymphoma, CNS lymphoma
PB2289: PRELIMINARY DATA FROM A FIRST-IN HUMAN PHASE II STUDY OF SEQUENTIAL USE OF SELINEXOR AND CD19 CHIMERIC ANTIGEN RECEPTOR MODIFIED T-CELL THERAPY (CART19) IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMA
Authors: Ying Zhang, Xiangping Zong, Jiaqi LI, Sixun Jia, Hongzhi Geng, Liangyu Zeng, Qin Yang, Wenzhi Cai, Shuangzhu Liu, Yutong Lu, Lei Yu, Caixia LI, Depei Wu
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Preclinical trial has demonstrated that sequential use of Selinexor and Anti-CD19 directed chimeric antigen receptor modified T-Cell therapy (CART19) cells might improve the anti‐tumor efficacy of CART 19 cells against lymphoma cells. However, the efficacy and safety of CART19 combined with Selinexor in lymphoma patients is unknown. We report preliminary data from a phase 2 trial of sequential use of Selinexor and CART19 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Aims: This clinical study sequential use of Selinexor and CART19 was initiated with the aim of prolong relapse-free survival of CART19 cells therapy in R/R B-NHL patients. Methods: We performed a multicenter, prospective, phase II, open-label clinical study of sequential use of Selinexor and CART19 in R/R B-NHL. Patients received Selinexor as a bridging therapy (40-60mg) with a weekly for three weeks prior to CART19 infusion. Over all response (ORR), duration of response (DOR) and safety were evaluated as primary objectives. This study is registered with ClinicalTrials.gov, NCT05322330. Results: Between February 10, 2022, and February 10, 2023, 6 patients were enrolled. Four patients with diffuse large B-cell lymphoma, one mantle cell lymphoma and one Burkitt lymphoma received Selinexor 40mg and CART19 treatment. The median age was 55.5 years (range 34-77), 3 (50.0%) of 6 patients had refractory disease, 5 (83.3%) of 6 patients had extranodal involvement and the median prior systemic therapy was 2 (range 2-5), 5 (83.3%) of 6 patients had evaluated LDH prior to Selinexor administration. Median on-study follow-up was 9.68 months (range 2.53-12.17). 4 (66.7%) of 6 patients had an overall response. Cytokine release syndrome (CRS) was the most common adverse event, occurring in all 6 (100.0%) patients [66.7% was grade 1-2 and 33.3% was grade 3]. No neurotoxicity was observed. The most common grade 3-4 adverse events were neutropenia (5 [83.3%] of 6 patients), thrombocytopenia (4 [66.7%]), and anemia (3 [50.0%]). No treatment-related grade 5 adverse event occurred. Furthermore, our data showed that the use of Selinexor resulted in a higher proportion of CD8+central memory T cell phenotypes (P=0.04) while having no effect on CD4+ central memory T cell phenotypes (Figure 1). Summary/Conclusion: These results demonstrated that sequential use of Selinexor and CART19 in R/R B-NHL is effective and well tolerated in patients with R/R B-NHL. This study is ongoing and patients being recruited, more results should be evaluated in future.Figure 1. Selinexor significantly increased the proportion of CD8+ central memory T cells (CD3+CD8+CCR7+CD45RA-). Keywords: CAR-T, B cell lymphoma
PB2158: RELAPSING/REFRACTORY ABDOMINAL WALL EXTRA-MEDULLARY PLASMACYTOMAS DEMONSTRATING A RAPID COMPLETE RESPONSE TO BELANTAMAB MAFODOTIN
Authors: Mohamed Ali, Rehman Faryal, Roseann O Doherty, Khalid Saeed, Peter O’gorman
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: A 71-year-old male was diagnosed in November 2018 with Symptomatic Multiple Myeloma. Baseline investigations showed IgG Kappa para-protein of 31 g/L, FISH analysis failed as bone marrow plasma cells <10%. CT PET scan showed a large sternal mass 9x9.7x7 cm, SUV max. of 7.6 with left 8th rib lesion, SUV max of 7.8. He received standard RVD (Revlimid, Velcade and Dexamethasone) regimen for 7 cycles with very good partial response (VGPR). Paraprotein decreased to 3g/l however there was only slight reduction in plasmacytoma size to 9x8.5x4 with SUV max 7.3. He was switched to KRD (Carfilzomib, Revlimid and Dexamethasone) along with radiotherapy to the sternal lesions with very good response biochemically (SPEP, normal pattern) and radiologically (repeat CT PET scan showed no metabolically active disease with no residual mass). He proceeded to ASCT in March 2020.High risk maintenance was commenced with Lenalidomide + Velcade, however, after 4 months he showed radiological relapse. The treatment was switched to DVD (Daratumumab, Velcade and Dexamethasone) with very good partial response. In July 2021, he noticed multiple small lesions about 0.5-1 cm on the abdominal wall. Biopsy confirmed clonal plasma cells in the abdominal wall subcutaneous fat. The lesions were resolved with local radiotherapy. Aims:Methods: In October 2021 shortly after COVID booster vaccine, the abdominal wall lesions markedly increased in size and number making a confluent group of nodules approximately 20cm x 15cm.He was commenced on Belantamab through the compassionate access program in December 2021. After completing 2 cycles, the nodules completely resolved. At the end of June 2022, he exhibited a biochemical relapse and re-imaging showed new sub centimeter Lymphadenopathy, but no recurrence of the abdominal wall lesions. Results: Our patient showed a complete response of extramedullary Myeloma to BELANTAMAB Summary/Conclusion: The extramedullary phase of Myeloma remains a major medical challenge and further studies are required to clarify the role of antibody-drug conjugates.Keywords: Plasma cells, Multiple myeloma
PB2365: CHILDHOOD BURKITT LYMPHOMA: ABOUT 31 CASES (EXPERIENCE OF THE PEDIATRIC CLINICAL HEMATOLOGY DEPARTMENT OF AZIZA OTHMANA’S HOSPITAL)
Authors: Nefzi Rihab, Marwa Bahri, Hamida Khémiri Guerbouj, Ameni Yahia, Raihane Ben Lakhal, Yosr Ben Abdennabi, Lamia Aissaoui
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Burkitt lymphoma (BL) is a rare hematological malignancy. Although the incidence of BL is low, it is one of the most common types of non-Hodgkin lymphoma in children. Three clinical variants of BL are recognized, including endemic BL, sporadic BL and immunodeficiency-associated BL. Aims: Our study is made to investigate the demographic characteristics and treatment outcomes on overall survival and relapse free survival. Methods: It was a retrospective monocentric study, enrolled Thirty-one cases of initially diagnosed Burkitt lymphoma of children (age ≤18 years) in the pediatric clinical hematology department of Aziza Othmana's Hospital from January 2005 to December 2021. Results: The median age at the time of diagnosis was 8.7 years [2 -17]. The sex ratio was 2.8(23 boys and 8 girls). First symptoms were cervical adenopathy in 13 patients (41.9%), exophthalmia in 4 (12.9%), abdominal pain in 3 (9.7%), upper dyspnea in 3 (9.7%), bone pain in 2patients(6.5%), headache in 2(6.5%),oral tumefaction in 2 (6.5%),femoral thrombophlebitis in one (3.2%),odynophagia in one (3.2%). According to Murphy's classification,2 patients were classified in stage I, 7 in stage II,4 in stage III,18 in stage VI. Bone marrow invasion was found in 11 patients (35.5%) and central nervous system damage in 10 (32%). t(8;14) was found in only 3 patients. All patients were treated according to the LMB 2001 protocol modified in 2003.Fifteen patients were enrolled in group B, 5 in group C1 and 11 in group C3. 27 patients (87%) had complete response. 4 patients were in progression at 2.5 months [2-3] from the start of treatment followed by death despite salvage therapy. Treatment-related mortality was 7.5% (2/27 patients): 1 Klebsiella pneumoniae bacterial meningitis at day 10 of COPADEM1,1 gastrointestinal bleeding at day 25 of CYVE1. Overall survival (OS) at 120 months is 80.6%. OS at 120 months for stages I and II is 100%, stage III is 75% and stage IV is 72,2%. Relapse free survival at 120 months is 100 %. Summary/Conclusion: BL is a highly aggressive lymphoma potentially curable although toxicity related mortality is important. Several factors influence overall survival mainly the initial aggressive character, compliance with the dose-intensity effect and control of infectious complications. For further verification, a large sample multicenter randomized controlled study should be performed to better explore the different survival factors. Keywords: Survival, Chemotherapy, Children, Burkitt's lymphoma
PB2143: PROGNOSTIC SIGNIFICANCE AND CLINICAL APPLICABILITY OF THE COMORBIDITY INDICES IN PATIENTS WITH MULTIPLE MYELOMA: IMWG AND SARC-F SCORE
Authors: Nikola Vukosavljevic, Zoran Milojevic, Katarina Markovic, Aleksandra Sretenovic, Marko Mitrovic, Nevenka Markovic, Dusica Davidovic, Miroslav Pavlovic, Tijana Markovic-Dobrijevic, Marija Cakarevic, Jelena Bila
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Contemporary treatment of multiple myeloma (MM) is individually tailored to the patient’s profile. Aims: The goal of study was to analyse the prognostic significance and clinical applicability of the International Working Group (IMWG) comorbidity index, and the SARC-F score for sarcopenia. Methods: Study included 48 newly diagnosed MM patients (pts, male/female: 19/29, median age 67 years, range 43-84 years), predominantly with IgG MM (29pts; 60.4%), in III CS (D&S; 33pts, 68.7%) with R-ISS 2 (22pts; 45.8%), and renal impairment in 14pts (29.1 %). Bortezomib-based treatment had 19pts (40.4%), and Thalidomide-based 29pts (59.6%). In 10pts (20.8%), autologous stem cell transplantation (ASCT) was performed. Patients were analyzed according to the IMWG and SARC-F scores of aging and eligibility for intensive treatment. Results: According the SARC-F score, 35pts (72.9%) had sarcopenia. Of those, only 2pts were treated with ASCT (p=0.00002). According to the IMWG score, majority were “frail” patients (23pts, 47.9%). The IMWG index had a strong prognostic significance on ASCT eligibility (p=0.005). “Fit” and intermediate “fit” pts, had significantly better 5-year overall survival (OS) compared to the “frail” population (70% vs 24.5%, p=0.02). Majority of patients with sarcopenia (18pts, 62.2%) had OS <5 years. A strong correlation of IMWG and SARC-F scores was proven (p=0.0008). There was no correlation of IMWG and/or SARC-F scores and: clinical stage (DSS), prognostic indices (ISS; R-ISS), treatment-response, or progression-free survival (p>0.05). Summary/Conclusion: IMWG and SARC-F scores have a clear prognostic significance and clinical applicability, with an impact on the treatment approach in MM patients. Keywords: International prognostic index, Comorbidities, Multiple myeloma, Prognosis
PB2288: INCIDENCE OF NEWLY DIAGNOSED AGGRESSIVE NON-HODGKIN’S LYMPHOMA BEFORE AND DURING THE COVID-19 PANDEMIC IN ISRAEL - A SINGLE CENTER RETROSPECTIVE STUDY
Authors: Yotam Bronstein, Eugene Feigin, Irit Avivi, Erel Joffe, Chava Perry
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: As part of the general objections of certain subgroups to Coronavirus disease 2019 (COVID-19) vaccination, concerns have been raised that the vaccine and/or the viral infection itself propagate an increased incidence of lymphoma. Aims: To analyze trends in the incidence of newly diagnosed aggressive non-Hodgkin’s lymphoma (NHL) before and during the COVID-19 pandemic and prior and following the implementation of nation-wide vaccination. Methods: We retrospectively reviewed data of all patients diagnosed and treated for aggressive NHL between 9/2017 and 8/2022. Cases were identified by a combination of presence of a new ICD-9 diagnosis of an aggressive lymphoma and administration of a CHOP/CHOP-like chemotherapy regimen. The cohort was divided into two 30-month periods: ‘pre-pandemic’ 9/2017-2/2020 and ‘COVID-19’ 3/2020-8/2022. The ‘COVID-19’ period was further divided into two 15m periods - ‘pre-vaccine’ (until 5/2021) also representing the era of major quarantine, and ‘post-vaccine’ which represents the time after the administration of the first mRNA COVID-19 vaccine and the following vaccine boosters. The baseline demographic and characteristics and the clinical outcomes were extracted from the patients’ electronic medical records. Throughout all periods our clinic was open for frontal visits. Results: During the study, a total of 535 patients (46.5% women) were diagnosed with aggressive NHL. The median (IQR) age was 68.2 (56.5-75.2) years; 284 (53.1%) new aggressive NHL cases were observed in the pre-pandemic period and 251 (46.9%) in the COVID-19 period (Figure 1); no statistical difference was observed (p=0.4). Baseline demographics and disease characteristics were similar between the two periods. Histological subtypes were similar between the periods (94.0% vs. 92.4% B-cell NHLs, p=0.5; of which 9.4% vs. 9.1% represented a transformation from a prior mature B cell lymphoma, p=0.9). There was no difference in the 1-year overall survival between groups (84.0% vs. 78.7%, p=0.5). Comparing the pre-vaccine and post-vaccine epochs during the COVID-19 pandemic, there was no clear increase in the incidence of newly diagnosed aggressive NHL patients. Moreover, there was no difference in the rate of hospitalization for severe COVID-19 between these sub-groups (5.6% n=8 vs. 6.4% n=7, p=0.8). Summary: We did not observe a significant increase in the incidence of new cases of aggressive lymphomas following the COVID-19 pandemic or the institution of a national vaccination program. Figure 1: Incidence of newly diagnosed aggressive non-Hodgkin’s lymphoma before and during the COVID-19 pandemic in Israel.Keywords: High-grade non-Hodgkins-lymphoma, Lymphoma, Non-Hodgkin’s lymphoma, COVID-19